The Chicago Breast Cancer SPORE program brings together a multidisciplinary team of basic, clinical and population science investigators at the University of Chicago to design innovative research that will reduce the "pain and suffering" from breast cancer using a uniquely global strategy. The translational research projects chosen represent extensions of funded research being conducted by SPORE investigators. The science of the SPORE consists of four translational research projects. Project 1 "Estimation of Breast Cancer Risk from Mammography and Breast MRI" will develop multi-modality, image-based markers for assessing breast density and parenchymal structure that may be used alone or in combination with clinical measures and other biomarkers to quantify breast cancer risk and for monitoring response to chemopreventive agents. Project 2 "Specificity of MRI with optimal temporal, spatial, and spectral sampling in early breast cancer" will examine whether MR imaging with improved spectral, temporal and spatial sampling (MRITSS) leads to improved anatomic and functional imaging in the high-risk population that would benefit most from MRI. Project 3: "Variation in hormone and xenobiotic metabolizing enzyme genes and breast cancer risk" will determine whether sequence variation in genes involved in the metabolism of sex hormones and xenobiotics influence the risk to breast cancer using resources from existing case-control cohorts that are highly enriched for women of African ancestry with ER negative breast cancer. Project 4: "ldentifying population specific variants important in toxicity to breast cancer chemotherapy" to identify genetic variation in target genes that result in an increased risk of toxicities using capecitabine and platinating agents as model drugs. We will identify genetic variants that dictate phenotypes including cytotoxicity and apoptosis by utilizing EBV-transformed lymphoblastoid cell lines from related healthy Caucasians and follow up with studies in African Americans and Yoruban trios from Nigeria. These research projects will be supported by three scientific cores: Core 1: SPORE Administration, Core 2: Biospecimens, Pathology and Genotyping, and Core 3: Analytic and Bioinformatics Core. A Developmental Research Program will advance the rapid translation of the most promising scientific discoveries to the clinic and support the reverse translation of clinical observations in the laboratory. A Career Development Program will be used to support the transition of the most promising junior faculty investigators and to recruit new senior investigators into breast cancer translational research. The investigators, core facilities, the career development and the developmental research programs in the SPORE are all integrated into the University of Chicago Cancer Research Center and, collectively, will translate scientific advances into substantial improvement in breast cancer outcomes.